Early Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort.

Aims: Gestational diabetes mellitus (GDM) poses a significant risk for developing type 2 diabetes mellitus (T2D) and exhibits heterogeneity. However, understanding the link between different types of post-GDM individuals without diabetes and their progression to T2D is crucial to advance personalised medicine approaches.

Materials And Methods: We employed a discovery-based unsupervised machine learning clustering method to generate clustering models for analysing metabolomics, clinical, and biochemical datasets.

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.

RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within or near that gene. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function.

Accessing iridium Cp* as a cofactor for artificial metalloenzymes.

By introducing new-to-nature transformations, artificial metalloenzymes hold great potential for expanding the biosynthetic toolbox. The chemistry of an active cofactor in these enzymes is highly dependent on how the holoprotein is assembled, potentially limiting the choice of organometallic complexes amenable to incorporation and ability of the protein structure to influence the metal centre. We have previously reported a method utilising ligand exchange as a means to introduce ruthenium-arene fragments into a four-helix bundle protein.

Reduced circulating sphingolipids and activity are linked to T2D risk and impaired insulin secretion.

Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the allele of the gene in Hispanic women shortly after a GDM pregnancy.

Bayesian Gene Set Benchmark Dose Estimation for "omic" responses.

Motivation: Estimating a toxic reference point using tools like the benchmark dose (BMD) is a critical step in setting policy to regulate pollution and ensure safe environments. Toxicity can be measured for different endpoints, including changes in gene expression and histopathology for various tissues, and is typically explored one gene or tissue at a time in a univariate setting that ignores correlation. In this work, we develop a multivariate estimation procedure to estimate the BMD for specified gene sets.